Epidermal Growth Factor (EGF) is a 6045 M. W. (53 residue) polypeptide originally isolated from the submaxillary gland of the adult male mouse. The amino acid sequence, location of the three disulfide bonds and physical properties of this hormone have been determined. A similar polypeptide, human EGF, has been isolated from urine. Human EGF is probably identical to the anti gastric-acid secretory hormone urogastrone. EGF stimulates the growth of epidermis and corneal epithelium in a variety of species, both in organ culture and in vivo. It also is a growth factor for many cell types in tissue culture. The overall objectives of the proposed studies are to elucidate the biological significance of the presence in man (and other higher organisms) of both EGF and cellular receptors for the peptide. We plan to study (a) biochemical nature of the interaction of labeled-EGF with responsive cells, (b) the fate of both the hormone and its receptor, (c) the biochemical mechanisms by which EGF controls the growth of cells and (d) the normal physiological function and clinical usefulness of this hormone. The interaction of the hormone with intact cells will be examined using EGF labeled with 125I, fluorescein, and ferritin. The interaction of the hormone with its membrane receptor also will be studied using specific membrane impermeable cross linking reagents. Attempts will be made to detect membrane alterations induced by the binding of EGF.